Identification

Name
Anidulafungin
Accession Number
DB00362  (APRD01301)
Type
Small Molecule
Groups
Approved, Investigational
Description

Anidulafungin or Eraxis is an anti-fungal drug manufactured by Pfizer that gained approval by the Food and Drug Administration (FDA) in February 21, 2006; it was previously known as LY303366. There is preliminary evidence that it has a similar safety profile to caspofungin. [Wikipedia]

Structure
Thumb
Synonyms
  • (4R,5R)-4,5-Dihydroxy-N²-[[4''-(pentyloxy)-p-terphenyl-4-yl]carbonyl]-L-ornithyl-L-threonyl-trans-4-hydroxy-L-prolyl-(S)-4-hydroxy-4(p-hydroxyphenyl)-L-threonyl-L-threonyl-(3S,4S)-3-hydroxy-4-methyl-L-proline cyclic (6->1)-peptide
  • Anidulafungin
  • Anidulafungina
  • Anidulafungine
  • Anidulafunginum
  • N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2R)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.09,13]heptacosan-18-yl]- 4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide
  • V-Echinocandin
External IDs
LY-303366 / LY-307853 / LY-329960 / LY-333006 / LY303366 / VEC / VER-002
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EraxisPowder, for solution100 mgIntravenousPfizer2010-01-25Not applicableCanada
EraxisKit50 mg/15mLPfizer Inc.2007-05-152007-05-15Us
EraxisInjection, powder, lyophilized, for solution50 mg/15mLIntravenousRoerig2006-02-17Not applicableUs
EraxisPowder, for solution100 mgIntravenousPfizer2008-01-252013-07-19Canada
EraxisKit100 mg/30mLPfizer Inc.2007-05-152007-05-15Us
EraxisInjection, powder, lyophilized, for solution100 mg/30mLIntravenousRoerig2006-02-17Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gd-anidulafunginPowder, for solution100 mgIntravenousGenmed A Division Of Pfizer Canada IncNot applicableNot applicableCanada
International/Other Brands
Ecalta (Pfizer) / Eraxis
Categories
UNII
9HLM53094I
CAS number
166663-25-8
Weight
Average: 1140.2369
Monoisotopic: 1139.506293945
Chemical Formula
C58H73N7O17
InChI Key
JHVAMHSQVVQIOT-MFAJLEFUSA-N
InChI
InChI=1S/C58H73N7O17/c1-5-6-7-24-82-40-22-18-35(19-23-40)33-10-8-32(9-11-33)34-12-14-37(15-13-34)51(74)59-41-26-43(70)54(77)63-56(79)47-48(71)29(2)27-65(47)58(81)45(31(4)67)61-55(78)46(50(73)49(72)36-16-20-38(68)21-17-36)62-53(76)42-25-39(69)28-64(42)57(80)44(30(3)66)60-52(41)75/h8-23,29-31,39,41-50,54,66-73,77H,5-7,24-28H2,1-4H3,(H,59,74)(H,60,75)(H,61,78)(H,62,76)(H,63,79)/t29-,30+,31+,39+,41-,42-,43+,44-,45-,46-,47-,48-,49-,50-,54+/m0/s1
IUPAC Name
N-[(3S,6S,9S,11R,15S,18S,20R,21R,24S,25S,26S)-6-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-3,15-bis[(1R)-1-hydroxyethyl]-26-methyl-2,5,8,14,17,23-hexaoxo-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0⁹,¹³]heptacosan-18-yl]-4-{4-[4-(pentyloxy)phenyl]phenyl}benzamide
SMILES
[H][C@@]12C[C@@H](O)CN1C(=O)[C@@]([H])(NC(=O)[C@H](C[C@@H](O)[C@@H](O)NC(=O)[C@]1([H])[C@@H](O)[C@@H](C)CN1C(=O)[C@@]([H])(NC(=O)[C@@]([H])(NC2=O)[C@H](O)[C@@H](O)C1=CC=C(O)C=C1)[C@@H](C)O)NC(=O)C1=CC=C(C=C1)C1=CC=C(C=C1)C1=CC=C(OCCCCC)C=C1)[C@@H](C)O

Pharmacology

Indication

For use in the treatment of the following fungal infections: Candidemia and other forms of Candida infections (intra-abdominal abscess, and peritonitis), Aspergillus infections, and esophageal candidiasis. Also considered an alternative treatment for oropharyngeal canaidiasis.

Associated Conditions
Pharmacodynamics

Anidulafungin is a semi-synthetic lipopeptide synthesized from a fermentation product of Aspergillus nidulans. Anidulafungin is an echinocandin, a class of antifungal drugs that inhibits the synthesis of 1,3-β-D-glucan, an essential component of fungal cell walls. Anidulafungin is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes.

Mechanism of action

Anidulafungin is a semi-synthetic echinocandin with antifungal activity. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall, ultimately leading to osmotic instability and cell death.

TargetActionsOrganism
A1,3-beta-glucan synthase component FKS1
inhibitor
Aspergillus niger (strain CBS 513.88 / FGSC A1513)
Absorption
Not Available
Volume of distribution
  • 30 to 50 L
Protein binding

84%

Metabolism

Hepatic metabolism of anidulafungin has not been observed. Anidulafungin is not a clinically relevant substrate, inducer, or inhibitor of cytochrome P450 (CYP450) isoenzymes. Anidulafungin undergoes slow chemical degradation at physiologic temperature and pH to a ring-opened peptide that lacks antifungal activity.

Route of elimination

Less than 1% of the administered radioactive dose was excreted in the urine. Anidulafungin is not hepatically metabolized.

Half life

40-50 hours

Clearance
  • 1 L/h
Toxicity

During clinical trials a single 400 mg dose of anidulafungin was inadvertently administered as a loading dose. No clinical adverse events were reported. The maximum non-lethal dose of anidulafungin in rats was 50 mg/kg, a dose which is equivalent to 10 times the recommended daily dose for esophageal candidiasis (50mg/day).

Affected organisms
  • Candida albicans and other yeasts
  • Aspergillis, Candida and other fungi
  • Candida parapsilosis
  • Coolia tropicalis
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Scott Jenkins, Gary Liversidge, Deborah Neville, "Nanoparticulate Anidulafungin Compositions and Methods for Making the Same." U.S. Patent US20090238867, issued September 24, 2009.

US20090238867
General References
  1. Cappelletty D, Eiselstein-McKitrick K: The echinocandins. Pharmacotherapy. 2007 Mar;27(3):369-88. [PubMed:17316149]
  2. Vazquez JA: Anidulafungin: a new echinocandin with a novel profile. Clin Ther. 2005 Jun;27(6):657-73. [PubMed:16117974]
  3. Grover ND: Echinocandins: A ray of hope in antifungal drug therapy. Indian J Pharmacol. 2010 Feb;42(1):9-11. doi: 10.4103/0253-7613.62396. [PubMed:20606829]
  4. Vazquez JA: The safety of anidulafungin. Expert Opin Drug Saf. 2006 Nov;5(6):751-8. [PubMed:17044802]
  5. Menichetti F: Anidulafungin, a new echinocandin: effectiveness and tolerability. Drugs. 2009;69 Suppl 1:95-7. doi: 10.2165/11315570-000000000-00000. [PubMed:19877741]
  6. Vazquez JA, Sobel JD: Anidulafungin: a novel echinocandin. Clin Infect Dis. 2006 Jul 15;43(2):215-22. Epub 2006 Jun 9. [PubMed:16779750]
  7. Estes KE, Penzak SR, Calis KA, Walsh TJ: Pharmacology and antifungal properties of anidulafungin, a new echinocandin. Pharmacotherapy. 2009 Jan;29(1):17-30. doi: 10.1592/phco.29.1.17. [PubMed:19113794]
  8. Morace G, Borghi E, Iatta R, Montagna MT: Anidulafungin, a new echinocandin: in vitro activity. Drugs. 2009;69 Suppl 1:91-4. doi: 10.2165/11315560-000000000-00000. [PubMed:19877740]
External Links
KEGG Drug
D03211
PubChem Compound
166548
PubChem Substance
46505616
ChemSpider
145752
BindingDB
50417554
ChEBI
55346
ChEMBL
CHEMBL264241
Therapeutic Targets Database
DAP000546
PharmGKB
PA164742938
Drugs.com
Drugs.com Drug Page
Wikipedia
Anidulafungin
ATC Codes
J02AX06 — Anidulafungin
AHFS Codes
  • 08:14.16 — Echinocandins
FDA label
Download (2.25 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableInfection NOS1
1CompletedTreatmentInvasive Fungal Infections1
1, 2CompletedSupportive CareInfection NOS / Neutropenias / Unspecified Childhood Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentNeutropenias1
2CompletedNot AvailableLeukemia Acute Myeloid Leukemia (AML) / Leukemias / Myelodysplastic Syndrome1
2CompletedTreatmentCandidiasis infection2
2TerminatedOtherRespiratory Tract Infections (RTI) / Ventilator-associated Bacterial Pneumonia1
2TerminatedPreventionMalignancies, Hematologic1
2Unknown StatusTreatmentAcute Renal Failure (ARF) / Infection NOS1
2, 3CompletedTreatmentAspergillosis1
2, 3RecruitingTreatmentChildhood Ependymoma1
3CompletedTreatmentAspergillosis1
3CompletedTreatmentCandidemia2
3CompletedTreatmentCandidiasis, Invasive1
3CompletedTreatmentCandidiasis infection1
3CompletedTreatmentCandidiasis infection / Prophylaxis of Candida Infections1
3TerminatedNot AvailableCandidemia1
3TerminatedTreatmentCandidiasis infection / Fungaemia / Neutropenias1
3WithdrawnTreatmentAspergillosis / Neuroaspergillosis / Pulmonary Invasive Aspergillosis1
4CompletedNot AvailableAspergillosis / Candidemia1
4CompletedNot AvailableObesity Morbid1
4CompletedOtherBMI >30 kg/m2 / Mycoses1
4CompletedPreventionCentral Nervous System Fungal Infections / Fungaemia / Lung Diseases, Fungal / Mycoses1
4CompletedTreatmentCandidemia / Candidiasis, Invasive1
4CompletedTreatmentInfections, Fungal / Liver Diseases1
4CompletedTreatmentCandidiasis infection1
4TerminatedTreatmentAspergillosis1
4Unknown StatusTreatmentCandidemia1
Not AvailableActive Not RecruitingNot AvailableSystemic Fungal Infections1
Not AvailableCompletedNot AvailableCandidiasis infection1
Not AvailableCompletedTreatmentCandidiasis, Invasive1

Pharmacoeconomics

Manufacturers
  • Vicuron pharmaceuticals inc
Packagers
  • Ben Venue Laboratories Inc.
  • Pfizer Inc.
  • Pharmacia Inc.
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous100 mg/30mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/15mL
Kit100 mg/30mL
Kit50 mg/15mL
Powder, for solutionIntravenous100 mg
Prices
Unit descriptionCostUnit
Eraxis(water dil) 100 mg vial216.0USD vial
Eraxis(water dil) 50 mg vial108.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7198796No2007-04-032022-06-13Us
US6384013No2002-05-072012-03-19Us
CA2362481No2008-11-042020-03-02Canada
CA2091663No2007-10-302013-03-15Canada
US5965525No1999-10-122020-02-17Us
US6960564No2005-11-012021-04-12Us
US7709444No2010-05-042021-04-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0564 mg/mLALOGPS
logP1.87ALOGPS
logP-1.5ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)9.46ChemAxon
pKa (Strongest Basic)-3.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area377.42 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity292.29 m3·mol-1ChemAxon
Polarizability122.38 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6513
Blood Brain Barrier-0.9833
Caco-2 permeable-0.7967
P-glycoprotein substrateSubstrate0.9066
P-glycoprotein inhibitor INon-inhibitor0.6298
P-glycoprotein inhibitor IIInhibitor0.6296
Renal organic cation transporterNon-inhibitor0.9085
CYP450 2C9 substrateNon-substrate0.7737
CYP450 2D6 substrateNon-substrate0.8428
CYP450 3A4 substrateSubstrate0.644
CYP450 1A2 substrateNon-inhibitor0.949
CYP450 2C9 inhibitorNon-inhibitor0.8978
CYP450 2D6 inhibitorNon-inhibitor0.8104
CYP450 2C19 inhibitorNon-inhibitor0.8827
CYP450 3A4 inhibitorNon-inhibitor0.8221
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8637
Ames testNon AMES toxic0.7638
CarcinogenicityNon-carcinogens0.8077
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7797 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9863
hERG inhibition (predictor II)Inhibitor0.6881
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / P-terphenyls / Macrolactams / N-acyl-alpha amino acids and derivatives / Biphenyls and derivatives / Benzamides / Benzoyl derivatives / Phenoxy compounds / Phenol ethers / 1-hydroxy-2-unsubstituted benzenoids
show 14 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Para-terphenyl / Terphenyl / N-acyl-alpha amino acid or derivatives / Macrolactam / Biphenyl / Alpha-amino acid or derivatives / Benzamide / Benzoic acid or derivatives
show 30 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
antibiotic antifungal drug, echinocandin, semisynthetic derivative, azamacrocycle, heterodetic cyclic peptide (CHEBI:55346)

Targets

Kind
Protein
Organism
Aspergillus niger (strain CBS 513.88 / FGSC A1513)
Pharmacological action
Yes
Actions
Inhibitor
General Function
1,3-beta-d-glucan synthase activity
Specific Function
Catalytic subunit of the 1,3-beta-glucan synthase. Synthesizes 1,3-beta-glucan, a major structural component of the cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling ...
Gene Name
fksA
Uniprot ID
A2QLK4
Uniprot Name
1,3-beta-glucan synthase component FKS1
Molecular Weight
216972.8 Da
References
  1. Sucher AJ, Chahine EB, Balcer HE: Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1. [PubMed:19724014]
  2. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, part 1. Am J Health Syst Pharm. 2006 Sep 15;63(18):1693-703. [PubMed:16960253]
  3. Morris MI, Villmann M: Echinocandins in the management of invasive fungal infections, Part 2. Am J Health Syst Pharm. 2006 Oct 1;63(19):1813-20. [PubMed:16990627]
  4. Ponton J: [The fungal cell wall and the mechanism of action of anidulafungin]. Rev Iberoam Micol. 2008 Jun;25(2):78-82. [PubMed:18473501]
  5. Quindos G, Eraso E, Javier Carrillo-Munoz A, Canton E, Peman J: [In vitro antifungal activity of micafungin]. Rev Iberoam Micol. 2009 Mar 31;26(1):35-41. doi: 10.1016/S1130-1406(09)70006-3. Epub 2009 May 7. [PubMed:19463275]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2018 13:38